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  • Review Article
  • Published:

The evolutionary genomics of pathogen recombination

Key Points

  • The frequency and rate of genetic recombination in several species, specifically in microbes and pathogens, is unknown.

  • For pathogens, the rate at which populations recombine can help to explain the dynamics of drug resistance and pathogenicity. Furthermore, recombination is necessary for genetic mapping and for the ability of population genetic studies to locate genes that underlie important phenotypes (for example, genes that are associated with virulence, transmission and immune evasion). Finally, although almost all organisms engage in some form of recombination, our understanding of why recombination occurs and is maintained remains controversial.

  • Recombination allows genomic sites or regions to have different evolutionary histories. As a result, the presence of recombination complicates phylogenetic reconstruction and several phylogenetic methods that are used to infer population parameters.

  • Several non-parametric methods are available to detect and estimate recombination in systems that do not conform to standard assumptions, such as having constant population size and an infinite number of sites. Many of these methods have successfully revealed the action of recombination in several viruses, and in bacterial and protozoan species.

  • Unlike non-parametric methods, model-based approaches allow the population recombination rate to be inferred.

  • Model-based estimates of the population recombination rate seem to be consistent with experimental estimates, at least in bacteria. Although species certainly vary, there seem to be some phylogenetic consistencies between recombination rates, relative to the population mutation rates, across broad phylogenetic groupings of taxa.

  • The rates of recombination are often substantial and are correlated with life history, such as endemicity in a population. It is reasonable to suggest that recombination has an active role in the life history and fitness of many pathogens.

Abstract

A pressing problem in studying the evolution of microbial pathogens is to determine the extent to which these genomes recombine. This information is essential for locating pathogenicity loci by using association studies or population genetic approaches. Recombination also complicates the use of phylogenetic approaches to estimate evolutionary parameters such as selection pressures. Reliable methods that detect and estimate the rate of recombination are, therefore, vital. This article reviews the approaches that are available for detecting and estimating recombination in microbial pathogens and how they can be used to understand pathogen evolution and to identify medically relevant loci.

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Figure 1: Recombination rates across eukaryotic taxa.
Figure 2: The effect of recombination on branch lengths.
Figure 3: Homoplasy in a data set of five sequences.
Figure 4: Recombination rates relative to mutation rates for bacterial, protozoan and viral loci.

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Acknowledgements

We thank J. Anderson, D. Haydon, C. Langley, G. McVean, K. Thorton and three anonymous reviewers for discussions and readings of this manuscript. P.A. is funded by a Wellcome Trust Fellowship.

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PlasmoDB

Glossary

LATERAL GENE TRANSFER

The transfer of DNA, frequently cassettes of genes, between organisms.

EFFECTIVE POPULATION SIZE

(Ne). The theoretical number of organisms or copies of a locus for which the genetic variation in a given sample of the organisms or copies can be explained solely by mutation and genetic drift. Ne is related to, but never exceeds, the actual population size (N).

GENETIC DRIFT

Random changes in allele frequency that result from the sampling of gametes from generation to generation.

TRANSDUCTION

The introduction of a gene into a target cell by a viral vector.

TRANSFORMATION

The uptake of DNA by a bacterium from the surrounding environment.

CONJUGATION

The transfer of DNA from a donor cell to a recipient cell that is mediated by direct cell–cell contact.

TEMPLATE-SWITCHING PROCESS

A process by which the reverse transcriptase will switch templates during the replication process. If two viral haplotypes are present in the host, this will result in a recombinant product.

FIXATION

The accumulation of a mutation to a frequency of 100% in a gene pool.

TAJIMA'S D

Summary statistic of the spectrum of allelic frequencies at different sites. An excess of rare variants indicates a recent reduction in variation either due to a selective sweep or an expanding population.

MOLECULAR CLOCK

The principle that any sequence has a near-constant rate of evolution in all branches of a clade, which means that the amount of sequence divergence between two sequences will be proportional to the amount of time elapsed since their shared ancestor existed.

HAPLOTYPE

The combination of alleles at several loci on a single chromosome.

LINKAGE MAPPING

Markers that are physically close to a locus of interest segregate 'tightly' with the locus and will statistically be more closely associated with the observed variance of a trait. This property can be used to detect association in a population between a genetic marker and a locus that contributes to a particular phenotype.

INFINITE SITES MODEL

A simple model of the inheritance of quantitative traits that assumes an infinite number of unlinked loci. As a result, it is possible to assume that mutations occur only once at a particular locus, and that the probability of a mutation occurring at a site has a Poisson distribution.

NON-PARAMETRIC METHODS

Statistical procedures that are not based on models or assumptions pertaining to the distribution of the variable.

PARAMETRIC METHODS

Estimators and procedures that are based on models.

ORTHOLOGOUS GENES

Homologous genes in different species, the lineage of which derives from a common ancestral gene without gene duplication or horizontal transmission.

PARALOGOUS GENES

Homologous genes that originated by gene duplication (for example, human α-globin and β-globin).

LINKAGE DISEQUILIBRIUM

(LD). The condition in which the frequency of a particular haplotype for two loci is significantly greater than that expected from the product of the observed allelic frequencies at each locus.

MONTE CARLO METHOD

The use of randomly generated or sampled data and computer simulations to obtain approximate solutions to complex mathematical and statistical problems.

GENE CONVERSION

The non-reciprocal transfer of information between homologous genes as a consequence of heteroduplex formation, followed by repair of mismatches in the heteroduplex. In this context, conversion is associated with two crossovers.

LIKELIHOOD METHOD

The use of a model to determine the most probable estimate of a parameter that best fits the observed data.

FINITE SITES MODEL

By contrast to the infinite sites model of evolution, in this model, multiple mutation events can occur at the same site.

SELECTIVE SWEEPS

As a positively selected allele rises to fixation, linked alleles will be maintained in the population; by contrast, alleles that are linked to the non-selected allele are lost from the population. The consequence of this selective sweep is usually a reduced variation around the selected locus.

FACULTATIVE ASEXUAL SPECIES

Species in which reproduction is known to occur asexually or sexually.

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Awadalla, P. The evolutionary genomics of pathogen recombination. Nat Rev Genet 4, 50–60 (2003). https://doi.org/10.1038/nrg964

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